Xu Pingping, Ye Weiping, Zhong Saiyi, Li Hong, Feng Eric, Lin Shu-Hong, Kuo Chieh-Ti, Liu Jie-Yu, Lin Young C
Laboratory of Reproductive and Molecular Endocrinology, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210, USA.
Mol Med Rep. 2010 Nov-Dec;3(6):983-90. doi: 10.3892/mmr.2010.370. Epub 2010 Sep 27.
Adipocytes account for more than 90% of human breast volume and secrete adipocytokines, which play a role in breast cancer development. Among the adipocytokines is leptin, which is secreted mainly by adipocytes and plays a key role in breast cancer development. Leptin expression is up-regulated in both obese and breast cancer patients, and promotes breast cancer cell growth. Exposure to environmental estrogens has also been found to be directly related to the development of breast cancer. Zeranol (Z) is a non-steroidal anabolic growth promoter with estrogenic activity that is widely used in the US beef industry due to its commercial benefits. Gossypol is a natural compound extracted from cottonseed that inhibits breast cancer growth, and is potentially a chemopreventive food component. This study focused on Z and bio-active Z-containing sera (ZS) collected from Z-implanted beef, and evaluated their adverse health risk to humans. We hypothesized that Z increases the risk of breast cancer in obese women. A cell proliferation assay, ELISA analysis, RT-PCR and Western blotting were performed to investigate the interaction of leptin, Z and (-)-gossypol in primary cultured normal human breast pre-adipocytes. The results indicated that Z and ZS stimulated the growth of pre-adipocytes isolated from normal human breast tissues by up-regulating cyclin D1 expression, while (-)-gossypol reversed this effect.
脂肪细胞占人类乳房体积的90%以上，并分泌脂肪细胞因子，这些因子在乳腺癌发展中发挥作用。脂肪细胞因子中的瘦素主要由脂肪细胞分泌，在乳腺癌发展中起关键作用。瘦素表达在肥胖患者和乳腺癌患者中均上调，并促进乳腺癌细胞生长。还发现接触环境雌激素与乳腺癌的发展直接相关。玉米赤霉醇（Z）是一种具有雌激素活性的非甾体合成代谢生长促进剂，因其商业效益而在美国牛肉行业广泛使用。棉酚是从棉籽中提取的一种天然化合物，可抑制乳腺癌生长，可能是一种化学预防食品成分。本研究聚焦于Z以及从植入Z的牛肉中收集的具有生物活性的含Z血清（ZS），并评估它们对人类的不良健康风险。我们假设Z会增加肥胖女性患乳腺癌的风险。进行了细胞增殖试验、ELISA分析、RT-PCR和蛋白质免疫印迹，以研究瘦素、Z和（-）-棉酚在原代培养的正常人乳腺前脂肪细胞中的相互作用。结果表明，Z和ZS通过上调细胞周期蛋白D1的表达刺激从正常人乳腺组织分离的前脂肪细胞的生长，而（-）-棉酚则逆转了这种作用。
